The aim of these experiments is to provide a quantitative model of lung inflammation, mediated by the endogenous proteases of lung phagocytes, which can be abrogated by means of aerosolized liposomes which will act as vectors for anti-proteases. Elaborating upon a new model for acute and chronic alveolitis in the rabbit, we will study tracheal aspirates from animals exposed to intratracheal zymosan particles, by biochemical and ultrastructural, cytochemical techniques. Lungs, tracheal aspirates and purified cells will be analyzed for collagenase, elastase, cathepsin G, cathepsin D, and histonase after their encounter with zymosan particles and/or activated complement components. The pattern will be studied of inhibition of these proteases by defined protease inhibitor (alpha 1-antitrypsin, pepstatin, leupeptin, antipain, etc.). We will determine both the complement and the granulocyte-dependence of this model lung inflammation, and how the balance between proteases and antiproteases determines such inflammatory stimuli as chemotaxis. After specific protease inhibitors, encapsulated in immunoglobulin coated liposomes, have been introduced to rabbit PMN and macrophages in vitro, we will study which are most effective at inhibiting intracellular and regurgitant proteases. These inhibitors will be entrapped in multilamellar and large unilamellar liposomes, and such liposomes, coated with aggregated rabbit IgG, will be instilled by Nebulizer into the experimentally inflamed lungs. Direct introduction via the airways should lead to the encounter of these Ig-coated vectors with the Fc receptor-bearing, inflammatory cells of the lung. Thus the phagocytes may be tricked into ingesting the means of their own disarmament. The ultimate goal is to provide a method for the treatment of genetic and acquired lung inflammation in man by means of inhaled liposome dispersions containing protease inhibitors.